We recently studied whether the endometrium of women with endometriosis might be abnormal during the implantation phase of the menstrual cycle. We evaluated the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis using a prospective observational study design. Twenty-four women with endometriosis and 23 healthy volunteers of similar age underwent an endometrial biopsy in the secretory phase and the immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 was evaluated. Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are progesterone dependent, these findings suggest the possibility of reduced endometrial progesterone action in this population. We have also examined the effect of the SPRM CDB-2914 on endometrium in the early luteal phase. Fifty-six women with regular cycles received a single dose of CDB-2914 (10, 50, or 100 mg) or placebo given after ovulation and within 2 days of the LH surge. Four to 6 days later, a transvaginal ultrasound scan measured endometrial thickness, and an endometrial biopsy specimen was obtained. The endometrium was evaluated by thickness and by immunohistochemical analysis for P-dependent markers;safety laboratory tests were performed, and E(2) and P levels were obtained. CDB-2914 caused a significant dose-dependent decrease in endometrial thickness, an increase in glandular P receptors, and a decrease in peripheral node addressins. Estradiol and P levels and menstrual cycle timing were not altered. No adverse effects were observed. The alteration in endometrial thickness and P-dependent markers of implantation in the absence of changes in hormone levels and cycle length suggests that CDB-2914 may have contraceptive properties.